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Details

Stereochemistry ACHIRAL
Molecular Formula C13H18Br2N2O.C9H10N4O4
Molecular Weight 616.303
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMBROXOL ACEFYLLINATE

SMILES

CN1C2=C(N(CC(O)=O)C=N2)C(=O)N(C)C1=O.NC3=C(Br)C=C(Br)C=C3CN[C@H]4CC[C@H](O)CC4

InChI

InChIKey=IPUHJDQWESJTGD-PFWPSKEQSA-N
InChI=1S/C13H18Br2N2O.C9H10N4O4/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10;1-11-7-6(8(16)12(2)9(11)17)13(4-10-7)3-5(14)15/h5-6,10-11,17-18H,1-4,7,16H2;4H,3H2,1-2H3,(H,14,15)/t10-,11-;

HIDE SMILES / InChI

Molecular Formula C9H10N4O4
Molecular Weight 238.2001
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C13H18Br2N2O
Molecular Weight 378.103
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800035262 | https://www.ncbi.nlm.nih.gov/pubmed/23158495 | https://www.ncbi.nlm.nih.gov/pubmed/18482096 | https://www.ncbi.nlm.nih.gov/pubmed/19578116 | http://zywiebio.com/drug-development/therapeutic-areas-of-interest/gaucher-disease/

Ambroxol, a substituted benzylamine, is an active metabolite of bromhexine, which is itself a synthetic derivative of vasicine, the active principle extracted from the plant species Adhatoda vasica. Ambroxol is an expectorant exerting mucokinetic properties, mucociliary activity, stimulation of surfactant production, anti-inflammatory and antioxidative actions and the local anaesthetic effect. Ambroxol was discovered at and has been manufactured by Dr. Karl Thomae GmbH, a division of Boehringer Ingelheim. The ambroxol patent is expired and the drug is available as a generic product from many different companies. Ambroxol was originally developed by Boehringer Ingelheim as a OTC therapy for respiratory disorders related to excessive mucus. Ambroxol's indication is secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. Boehringer Ingelheim markets the product under various brand names such as Mucosolvan® and Lasolvan®. Ambroxol was identified and found to be a pH-dependent, mixed-type inhibitor of glucocerebrosidase (GCase). Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of Ambroxol to bind and stabilize the enzyme was confirmed. Ambroxol increases both the lysosomal fraction and the enzymatic activity of several mutant GCase variants. This profile of Ambroxol would allow to bind and stabilize GCase in the endoplasmic reticulum (thus preventing its degradation within endoplasmic reticulum), but without affecting GCase in the lysosomes (thus allowing it to degrade glucosylceramide). Indeed, studies showed that Ambroxol treatment significantly increased N370S and F213I mutant GCase activity and protein levels in fibroblasts originally obtained from Gaucher patients. Gaucher's disease is caused by the deficiency of glucocerebrosidase; ambroxol is a chaperone that acts by binding to and stabilising glucocerebrosidase. Zywie (formerly ExSAR Corporation) and Belrose Pharma are developing ambroxol hydrochloride (BEL 0218) for the treatment of type III Gaucher's disease. .

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
MUCOSOLVAN

Approved Use

MUCOSOLVAN (ambroxol hydrochloride) is indicated for secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.
PubMed

PubMed

TitleDatePubMed
Current perspectives on the prevention and management of chronic lung disease in preterm infants.
2003
[Efficacy of combined drug therapy using a macrolide antibiotic and an antihistamine for adult patients with chronic paranasal sinusitis].
2003 Apr
Pharmacokinetic properties of single-dose loratadine and ambroxol alone and combined in tablet formulations in healthy men.
2003 Aug
Determination of ambroxol hydrochloride in pure solutions and some of its pharmaceutical preparations under batch and FIA conditions.
2003 Aug
Simultaneous high-throughput determination of clenbuterol, ambroxol and bromhexine in pharmaceutical formulations by HPLC with potentiometric detection.
2003 Aug 8
Determination of ambroxol in human plasma using LC-MS/MS.
2003 Jun 1
In vitro inhibition of human neutrophil histotoxicity by ambroxol: evidence for a multistep mechanism.
2003 Oct
Inhibition of bleomycin-induced cell death in rat alveolar macrophages and human lung epithelial cells by ambroxol.
2003 Oct 1
Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).
2004
Ambroxol reduces LPS toxicity mediated by induction of alkaline phosphatases in rat lung.
2004 Aug
[Protective effects of ambroxol on lung injury during cardiacpulmonary bypass in patients undergoing valve replacement].
2004 Dec
In vitro and in vivo antioxidant activity of ambroxol.
2004 Dec
[A near-infrared diffuse reflectance analysis method for the noninvasive quantitative analysis of ambroxol hydrochloride tablets].
2004 Jan
Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.
2004 Jan
Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.
2004 Jan
[Clinical observation on Biyan Qingdu Granule and ambroxol hydrochloride in treating secretory otitis media].
2004 Jul
[Comparison of the effect of ambroxol and dexamethasone on the expression of pulmonary surfactant proteins in the fetal rat lungs].
2004 Jun
Oral sustained delivery of ambroxol from in situ-gelling pectin formulations.
2004 Mar 1
[Management of extensive burn accompanying severe inhalation injury].
2004 May
Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis.
2004 May
Determination of ambroxol in an automated multi-pumping pulsed flow system.
2005 Apr
Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain.
2005 Dec
Cell-specific modulation of surfactant proteins by ambroxol treatment.
2005 Feb 15
Effect of ambroxol, spirulina and vitamin-E in naphthalene induced cataract in female rats.
2005 Jan
The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol.
2005 Jun 13
Adsorptive stripping voltammetric determination of ambroxol.
2005 Mar
[Treatment of sore throat pain with ambroxol-containing lozenges. Results of a pharmacy supported patient questionnaire].
2005 Nov
Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.
2005 Sep 19
Differences in tidal breathing between infants with chronic lung diseases and healthy controls.
2005 Sep 8
The influence of ambroxol and capsaicin on the isolated rabbit bladder wall.
2005 Sep-Oct
[Ambroxol].
2006
Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis.
2006 Apr
The influence of variation of gastric pH on the gelation and release characteristics of in situ gelling pectin formulations.
2006 Apr 7
[Ambroxol-induced toxicoderma].
2006 Feb
D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells.
2006 Feb 1
Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.
2006 Feb 13
Ambroxol for the prevention of acute upper respiratory disease.
2006 Jun
[Atomization inhalation of ambroxol as an auxiliary therapy for severe pneumonia in neonates].
2006 Jun
Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.
2006 Mar 13
Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia.
2006 May 5
Nutritional supplements and infection in the elderly: why do the findings conflict?
2006 Nov 23
[Ambroxol-induced immune hemolytic anemia].
2006 Oct
Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents.
2007
In situ gelling pectin formulations for oral drug delivery at high gastric pH.
2007 Apr 20
Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use.
2007 Jan 26
Simultaneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC-MS/MS.
2007 Jul
Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).
2007 Jun 15
[Determination of ambroxol and clenbuterol in human plasma by LC-MS/MS method].
2007 Mar
Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats.
2007 May
Solid-state chemistry of ambroxol theophylline-7-acetate.
2007 May
Patents

Sample Use Guides

In Vivo Use Guide
Adults: daily dose of 30 mg (one Ambroxol tablet ) to 120 mg (4 Ambroxol tablets) taken in 2 to 3 divided doses Children up to 2 years: half a teaspoonful Ambroxol syrup twice daily Children 2 - 5 years: half a teaspoonful Ambroxol syrup 3 times daily Children over 5 years: One teaspoonful Ambroxol syrup 2-3 times daily.
Route of Administration: Oral
Ambroxol exerted a biphasic response in surfactant secretion, with a significant increase at low concentrations (1 - 10 uM) and an inhibition at high concentrations (≥ 0.1 mM), which is beyond reported plasma Ambroxol concentrations in blood
Substance Class Chemical
Created
by admin
on Fri Dec 15 19:14:33 GMT 2023
Edited
by admin
on Fri Dec 15 19:14:33 GMT 2023
Record UNII
0HM1E174TN
Record Status Validated (UNII)
Record Version
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Name Type Language
AMBROXOL ACEFYLLINATE
MART.   WHO-DD  
Common Name English
Ambroxol Theophyllinate [WHO-DD]
Common Name English
ACEBROPHYLLINE
Common Name English
AMBROMUCIL
Common Name English
7H-PURINE-7-ACETIC ACID, 1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-, COMPD. WITH TRANS-4-(((2-AMINO-3,5-DIBROMOPHENYL)METHYL)AMINO)CYCLOHEXANOL (1:1)
Systematic Name English
AMBROXOL THEOPHYLLINATE
Common Name English
BRONCOMNES
Common Name English
SURFOLASE
Common Name English
CYCLOHEXANOL, 4-(((2-AMINO-3,5-DIBROMOPHENYL)METHYL)AMINO)-, TRANS-, MONO(1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-7H-PURINE-7-ACETATE) (SALT)
Systematic Name English
AMBROXOL ACEFYLLINATE [MART.]
Common Name English
AMBROXOL-THEOPHYLLINE-7-ACETATE
Common Name English
Ambroxol acefyllinate [WHO-DD]
Common Name English
Code System Code Type Description
RXCUI
186010
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
ALTERNATIVE
RXCUI
236595
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY RxNorm
FDA UNII
0HM1E174TN
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY
CAS
96989-76-3
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY
DRUG BANK
DB13141
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY
EVMPD
SUB12842MIG
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY
EPA CompTox
DTXSID60914235
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY
SMS_ID
100000089018
Created by admin on Fri Dec 15 19:14:33 GMT 2023 , Edited by admin on Fri Dec 15 19:14:33 GMT 2023
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY